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Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: Implication in the pathogenesis of Alzheimer’s disease

Original Research

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Authors: Gjumrakch Aliev, Eldar Gasimov, Mark E Obrenovich, Kathryn Fischbach, Justin C Shenk, et al

Published Date June 2008 Volume 2008:4(3) Pages 721 - 730
DOI: http://dx.doi.org/10.2147/VHRM.S2608

Gjumrakch Aliev1, Eldar Gasimov2, Mark E Obrenovich3, Kathryn Fischbach1, Justin C Shenk1, Mark A Smith3, George Perry3,4

1Department of Biology and 4College of Sciences, University of Texas at San Antonio, San Antonio, Texas, USA; 2Department of Histology and Embryology, Baku Medical University, Baku, Azerbaijan; 3Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA

Abstract: The pathogenesis that is primarily responsible for Alzheimer’s disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD biopsy samples and two transgenic mouse models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which overexpress human amyloid beta precursor protein (AβPP). In situ hybridization using probes for normal and 5 kb deleted human and mouse mitochondrial DNA (mtDNA) was performed along with immunocytochemistry using antibodies against the Aβ peptide processed from AβPP, 8-hydroxy-2’-guanosine (8OHG), and cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as well as mitochondrial DNA deletions and structural abnormalities were present in the vascular walls of the human AD samples and the AβPP-YAC and C57B6/SJL Tg (+) transgenic mice compared to age-matched controls. Ultrastructural damage in perivascular cells highly correlated with endothelial lesions in all samples. Therefore, pharmacological interventions, directed at correcting the chronic hypoperfusion state, may change the natural course of the development of dementing neurodegeneration.

Keywords: atherosclerosis, Alzheimer’s disease, transgenic animals, brain hypoperfusion, vascular and mitochondrial lesions, electron microscopy








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